The objectives of the proposed research are to characterize kinetically and pharmacologically some of the active transport systems in the choroid plexus of the lateral ventricles that are responsible for the formation of the CSF and for the maintenance of the constancy of the composition of this fluid. The systems to be studied include those responsible for Na transport and their relationship to HCO3 and Cl balance, Mg transport, and the transport of organic cations such as the amines and various basic drugs. A study of the ability of a number of drugs including several saluretics, ATPase inhibitors, etc., singly and in combination, to inhibit the production of CSF will be completed. The ability to reduce CSF flow by more than the usual 50-60% accomplished with single agents may have marked significance in the treatment of hydrocephalus. V-C perfusion to measure CSF production will be used in the latter studies. The others will be done using the in situ isolated choroid plexus in a chamber technique. This technique permits studying both the secretory and transport activity of a segment of the choroid plexus with nerves and blood supply intact yet isolated from the extraneous influences of the surrounding brain tissue. Elucidation of the mechanisms of active transport by the choroid plexus may provide a basis for understanding the etiology of CNS disfunction, for more effective therapy of CNS disorders including hydrocephalus, as well as the therapy of CNS toxicities.